Transdermal delivery of medication is well known in the prior art. Transdermal patches are available for a number of drugs. Commercially available examples of transdermal patches include scopolamine for the prevention of motion sickness, nicotine for aid in smoking cessation, nitroglycerin for the treatment of coronary angina pain, and estrogen for hormonal replacement. Generally, these systems have drug reservoirs sandwiched between an impervious backing and a membrane face which controls the steady state rate of drug delivery. The systems usually are attached to the skin by an adhesive gel with the membrane face adjacent to the skin.
Transdermal medication has significant advantages over both hypodermic injection and oral administration. A transdermal patch can provide significantly greater effective blood levels of a beneficial drug because the drug is not delivered in spike concentrations as is the case with hypodermic injection and most oral administration. In addition, drugs administered via transdermal patches are not subjected to the harsh environment of the digestive tract. Hence, in principle, transdermal delivery provides a method for administrating drugs that would otherwise need to be administered via hypodermic injection or intravenous infusion because the drug is destroyed in the digestive tract or immediately absorbed by the liver. Conversely, the digestive tract and liver are not subjected to the drug in transdermal administration. Many drugs, such as aspirin, have an adverse effect on the digestive tract.
Prior art transdermal drug delivery systems may be divided into passive diffusion and active transport systems. Transdermal drug delivery by diffusion is by far the most common of the transdermal methods. The nicotine patch is an example of this method of delivery (U.S. Pat. No. 4,597,961 to Frank T. Etscorn). This process is based on presenting the medication in a high dose external to the dermis and allowing the chemical to diffuse into and through the skin. The degree of diffusion depends on the porosity of the skin, the size and polarity of the drug molecules, and the concentration gradient across the stratum corneum, the outermost layer of human skin. These factors generally limit this mode of delivery to a very small number of useful drugs with very small molecules or unique electrical characteristics.
There have been two types of systems proposed to overcome the limited range of compounds that may be administered transdermally. The first class of techniques are based on the disruption of the skin to remove the diffusion barrier. One such method is described in U.S. Pat. No. 3,964,482. This technique utilizes an array of needle like protrusions that penetrate the stratum corneum. The drug is delivered either through the needles or on the surface of the skin. In the this case, the drug flows along the outer surface of the "needle" through the hole in the stratum corneum created by the needle. The length of the needles utilized in this invention is just long enough to penetrate the stratum corneum. Since the stratum corneum does not contain blood vessels or nerve endings, the patient does not experience bleeding or discomfort from the penetration of the needles.
The second class of drug delivery system involve the active transport of the compounds across the skin. The active diffusion systems involve iontophoresis, electroporation and ultrasound to increase the migration of the drug across the skin barrier. These methods attempt to electrically assist diffusion of the medication or apply high frequency electrical pulses or sound waves to the skin to improve absorption. Unfortunately, the high cost and inconvenience of providing portable electrical equipment have limited the commercial application of such active systems.
While this device has been known for over 25 years, devices of this type have not been commercially successful. The disruption of the stratum corneum is not sufficient to render the skin sufficiently permeable to allow many compounds of interest to be administered transdermally. In addition, the disruption provided by beds of "needles" and the like does not permit reproducible drug flow across the disrupted area. The needles used to make the holes fill the holes, thus blocking drug delivery. Furthermore, even if the needles are removed, the small holes produced thereby rapidly close on removal of the needle assembly.
Accordingly, it is a general object of the present invention to provide an improved apparatus and method for disrupting the outer skin layers in a manner that permits the layers to become permeable to drugs and the like.
It is another object of the invention to provide a method for disrupting the skin layers such that the disrupted area remains permeable for a time that is sufficient to administer compounds through the skin.
It is another object of the invention to eliminate or greatly reduce the pain of drug delivery by present skin-penetrating devices, such as needles, fluid jets, etc.
It is another object of the present invention to provide a transdermal delivery system that does not rely on applied electric fields, yet allows drugs that could not previously be administered by passive diffusion to be so administered.
These and other objects of the present invention will become apparent to those skilled in the art from the following detailed description of the invention and the accompanying drawings.